TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31724	95395;95396;95397	chr2:178546066;178546065;178546064	chr2:179410793;179410792;179410791
N2AB	30083	90472;90473;90474	chr2:178546066;178546065;178546064	chr2:179410793;179410792;179410791
N2A	29156	87691;87692;87693	chr2:178546066;178546065;178546064	chr2:179410793;179410792;179410791
N2B	22659	68200;68201;68202	chr2:178546066;178546065;178546064	chr2:179410793;179410792;179410791
Novex-1	22784	68575;68576;68577	chr2:178546066;178546065;178546064	chr2:179410793;179410792;179410791
Novex-2	22851	68776;68777;68778	chr2:178546066;178546065;178546064	chr2:179410793;179410792;179410791
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-119
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.3633
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/Q	rs1322640877	-1.035	1.0	N	0.692	0.408	0.214338557667	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
K/Q	rs1322640877	-1.035	1.0	N	0.692	0.408	0.214338557667	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86017E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.7955	likely_pathogenic	0.8265	pathogenic	-0.568	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
K/C	0.8863	likely_pathogenic	0.8983	pathogenic	-0.79	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/D	0.9006	likely_pathogenic	0.9148	pathogenic	-0.476	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/E	0.7083	likely_pathogenic	0.7351	pathogenic	-0.378	Destabilizing	0.999	D	0.602	neutral	N	0.496103374	None	None	N
K/F	0.936	likely_pathogenic	0.9518	pathogenic	-0.372	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/G	0.8331	likely_pathogenic	0.8522	pathogenic	-0.919	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/H	0.5301	ambiguous	0.5658	pathogenic	-1.318	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/I	0.7673	likely_pathogenic	0.7932	pathogenic	0.337	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/L	0.7722	likely_pathogenic	0.8156	pathogenic	0.337	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/M	0.5359	ambiguous	0.58	pathogenic	0.267	Stabilizing	1.0	D	0.757	deleterious	N	0.474775826	None	None	N
K/N	0.7404	likely_pathogenic	0.7683	pathogenic	-0.621	Destabilizing	1.0	D	0.722	prob.delet.	N	0.503877496	None	None	N
K/P	0.9924	likely_pathogenic	0.9941	pathogenic	0.065	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/Q	0.3846	ambiguous	0.4196	ambiguous	-0.773	Destabilizing	1.0	D	0.692	prob.neutral	N	0.508475239	None	None	N
K/R	0.1257	likely_benign	0.1318	benign	-0.674	Destabilizing	0.999	D	0.601	neutral	N	0.476498893	None	None	N
K/S	0.7606	likely_pathogenic	0.7854	pathogenic	-1.252	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/T	0.4485	ambiguous	0.4562	ambiguous	-0.958	Destabilizing	1.0	D	0.784	deleterious	N	0.478632334	None	None	N
K/V	0.7426	likely_pathogenic	0.7663	pathogenic	0.065	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/W	0.9335	likely_pathogenic	0.9499	pathogenic	-0.259	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
K/Y	0.7893	likely_pathogenic	0.8304	pathogenic	0.083	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.